There has been much interest in converting isolated stem cells into functioning tissues and organs through artificial laboratory procedures. For example, one can differentiate pluripotent stem cells (PSCs) into cardiac cells that spontaneously beat. However, the practical therapeutic use of these cells has been limited due to tumor formation. See Lee et al. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat. Med. 2013; 19: 998-1004. Residual stem cells or other progeny are thought to cause the tumor growth. Reports indicate that the number of residual stem cells sufficient to produce tumors in beating cardiac cells differentiated from human pluripotent stem cells (hPSCs) are at levels that cannot be detected using standard fluorescently tagged antibodies and FACS. Thus, there is a need to identify methods of detecting these cells at very low concentrations in order to make quality control determinations.
Raman spectroscopy directs electromagnetic radiation (e.g., in laser light source) on a molecule and detects scattered electromagnetic radiation of a changed wavelength. Plotting the intensity of shifted electromagnetic waves versus frequency is called a Raman spectrum. When a molecule is in close proximity to certain surfaces such as silver and gold nanoparticles, the intensity of scattered waves dramatically increases, a phenomenon referred to as surface-enhanced Raman scattering (SERS). Qian et al. report in vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nature Biotechnology, 2008, 26, 83-90. Wang et al. report the detection of circulating tumor cells in human peripheral blood using surface-enhanced Raman scattering nanoparticles. Cancer Res. 2011, 71(5):1526-32. See also U.S. Pat. No. 7,588,827, and Published Patent Application Number 2013/0149247, 2010/0068806, and Isrealsen et al., Nanoparticle Properties and Synthesis Effects on Surface-Enhanced Raman Scattering Enhancement Factor: An Introduction, The Scientific World Journal, Volume 2015, Article ID 124582.
Pallaoro et al. report rapid identification by surface-enhanced Raman scattering of cancer cells at low concentrations flowing in a microfluidic channel. ACS Nano, 2015, 9 (4), pp 4328-4336.
Yang et al. report ultrasensitive surface-enhanced Raman scattering detection in common fluids. Proc Natl Acad Sci USA, 2016, 113:268-273. See also Yang et al. Chinese Patents CN 104387790 (2015) and CN 105199422 (2015).
References cited herein are not an admission of prior art.